The discovery of enormous Raman signals from roughened silver electrodes along with understanding of the electric field enhancement mechanism sparked the promise of powerful surface-enhanced Raman spectroscopies (SERS) (see, for example, Fleischmann et al. Chem. Phys. Lett. 1974, 26, 442; Moskovits Rev. Mod. Phys. 1985, 57, 783; Albrecht et al. J. Am. Chem. Soc. 1977, 99, 5215; Jeanmaire et al. J. Electroanal. Chem. 1977, 84, 1; Mahajan et al. Phys. Chem. Chem. Phys. 2010, 12, 10429; Lal et al. Chem. Soc. Rev. 2008, 37, 898; Graham Angew. Chem., Int. Ed. 2010, 49, 2). In particular, SERS enhancements as high as 1010-1014 derived from discrete gold nanocolloid assemblies, which amplify the electromagnetic field confined between closely coupled nanopairs, have permitted sensing of single molecules (see Schwartzberg et al. J. Phys. Chem. B 2004, 108, 19191; Hao et al. J. Chem. Phys. 2004, 120, 357; Kneipp et al. Phys. Rev. Lett. 1997, 78, 1667. Sztainbuch J. Chem. Phys. 2006, 125, 1. Le et al. Chem. Phys. Lett. 2004, 396, 393; Rodriguez-Lorenzo et al. J. Am. Chem. Soc. 2009, 131, 4616; Lim et al. Nat. Mater. 2010, 9, 60; Nie et al. Science 1997, 275, 1102; Xu et al. Phys. Rev. Lett. 1999, 4357; Xu et al. Phys. Rev. E 2000, 62, 4318; Wustholz et al. J. Am. Chem. Soc. 2010, 132, 10903). The ability to reproducibly control the interstitial regions of intense field amplification (so-called “hot spots”) for reliable detection and identification of single molecules is an aim for those working in the field.
One of the most critical issues for achieving reproducible hot spots is the control of the gap size between plasmonic structures with subnanometer precision. Despite this, most work has concentrated more on the fabrication of the nanoparticles than control of these gaps. Control of the subnanometer critical dimension over large areas to create such hot spots uniformly is nontrivial. Even more difficult is placing precisely within these junctions of ultrahigh field enhancement. The simplest and most studied system for the generation of such hot spots is through aggregation of nanoparticle colloids. Although a huge under-standing of colloid aggregates exists due to numerous experimental, theoretical, and computational studies over the past 30 years (Myers Surfaces, Interfaces and Colloids; Wiley-VCH: New York, 1999; Chapters 4, 5, and 10; Creighton Surface Enhanced Raman Scattering; Chang, R. K., Furtak, T. E., Eds.; Plenum: New York, 1982; p 315; Meakin The Fractal Approach to Heterogeneous Chemistry; Avnir, D., Ed.; Wiley: New York, 1989; p 131; Weitz et al. Phys. Rev. Lett. 1984, 52, 1433; Girard et al. Phys. Rev. Lett. 2006, 97, 100801; De Waele et al. Nano Lett. 2007, 7, 2004; Harris et al. J. Phys. Chem. C. 2009, 113, 2784; Matsushita The Fractal Approach to Heterogeneous Chemistry, Avnir, D., Ed.; Wiley: New York, 1989; p 161) their widespread adoption as a practical SERS substrate has so-far been hindered by irreproducible performance (see Li et al. Nano Lett. 2009, 9, 485; Jarvis et al. Anal. Bioanal. Chem. 2010, 397, 1893).
For example, aggregates formed through the “salting” of citrate-capped colloids tend to display poor control over size, gap, and topology, while organic monolayer-capped assemblies exhibit inconsistent and broad particle spacing (FIG. 7a) (Novotny et al. Principles of Nano-Optics; Cambridge University Press: Cambridge, UK, 2006; pp 378-419; Bernard et al. J. Phys. Chem. C 2007, 111, 18445); supposedly, “rigid” linking molecules such as DNA, biotin-streptavidin, or multivalent thiols (FIG. 7b) (Park et al. J. Phys. Chem. B 2006, 110, 12673; Li et al. Chem. Mater. 1999, 11, 23; Aslan et al. J. Phys. Chem. B 2004, 108, 15631; Feldheim Electrochem. Soc. Interface 2001, 22; Dammer et al. Phys. Chem. Chem. Phys 2009, 11, 5455) restrict access to the hot spot they define and have not been rigid in practice.
Despite this vast amount of work on coagulation aggregates, crucial control over both particle spacing and the placement of molecules in these hot spots while linking the SERS to plasmon modes by simultaneous measurements has not been carried out.